In addition to the ongoing problem of heroin abuse, prescription opioid abuse has been emerging as a serious public health concern. Although several medications currently exist for treating opioid dependence, various problems associated with their use make the search for alternative forms of pharmacotherapy important. Naltrexone, an opioid antagonist that is currently available in oral form, is approved for the treatment of opioid dependence. However, medication non-compliance has been a major obstacle to effective treatment. In our previous research, we demonstrated that an injectable depot formulation of naltrexone was effective in antagonizing heroin for 3-5 weeks, depending on dose. A subsequent randomized, placebo-controlled clinical trial of this medication further showed that treatment retention increased in a dose-related fashion, with 39% of patients in the placebo group, 60% of patients in the 192 mg naltrexone group, and 68% of patients in the 384 mg naltrexone group remaining in treatment at the end of the 2-month study period. These results support the safety and effectiveness of this strategy for the treatment of opioid dependence. The study described in the current application is designed to evaluate the effects of an even longer-lasting implantable formulation of naltrexone. The safety, effectiveness, and duration of action of the naltrexone implant in reducing the analgesic, respiratory, subjective, and performance effects of heroin will be measured in humans. Importantly, the psychological and behavioral changes that may accompany long-term blockade of opioid receptors will also be measured in the current application. Specifically, impulsive behavior will be measured before and repeatedly after administration of the naltrexone implant. The availability of this formulation of naltrexone provides us with the unique opportunity to determine prospectively in a longitudinal study whether blockade of opioid receptors per se is associated with reductions in impulsive behavior and whether loss of blockade is associated with a return to baseline levels of impulsivity. [unreadable] [unreadable] [unreadable]